Genotype–phenotype analysis of 4q deletion syndrome: Proposal of a critical region

Authors


  • How to Cite this Article: Strehle E-M, Yu L, Rosenfeld JA, Donkervoort S, Zhou Y, Chen T-J, Martinez JE, Fan Y-S, Barbouth D, Zhu H, Vaglio A, Smith R, Stevens CA, Curry CJ, Ladda RL, Fan Z (Jane), Fox JE, Martin JA, Abdel-Hamid HZ, McCracken EA, McGillivray BC, Masser-Frye D, Huang T. 2012. Genotype–phenotype analysis of 4q deletion syndrome: Proposal of a critical region. Am J Med Genet Part A. 158A:2139–2151.

Abstract

Chromosome 4q deletion syndrome (4q- syndrome) is a rare condition, with an estimated incidence of 1 in 100,000. Although variable, the clinical spectrum commonly includes craniofacial, developmental, digital, skeletal, and cardiac involvement. Data on the genotype–phenotype correlation within the 4q arm are limited. We present detailed clinical and genetic information by array CGH on 20 patients with 4q deletions. We identified a patient who has a ∼465 kb deletion (186,770,069–187,234,800, hg18 coordinates) in 4q35.1 with all clinical features for 4q deletion syndrome except for developmental delay, suggesting that this is a critical region for this condition and a specific gene responsible for orofacial clefts and congenital heart defects resides in this region. Since the patients with terminal deletions all had cleft palate, our results provide further evidence that a gene associated with clefts is located on the terminal segment of 4q. By comparing and contrasting our patients' genetic information and clinical features, we found significant genotype–phenotype correlations at a single gene level linking specific phenotypes to individual genes. Based on these data, we constructed a hypothetical partial phenotype-genotype map for chromosome 4q which includes BMP3, SEC31A, MAPK10, SPARCL1, DMP1, IBSP, PKD2, GRID2, PITX2, NEUROG2, ANK2, FGF2, HAND2, and DUX4 genes. © 2012 Wiley Periodicals, Inc.

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